Crystal structures and Hirshfeld surface analyses of hypoxanthine salts involving 5-sulfosalicylate and perchlorate anions

The main intermolecular interactions in the two title salts are O⋯H/H⋯O contacts, as revealed by Hirshfeld surface analyses.

Two salts of 1,9-dihydropurin-6-one (hypoxanthine), namely, 6-oxo-1,9-dihydropurin-7-ium 5-sulfosalicylate dihydrate, C 5 H 5 N 4 O + ÁC 7 H 5 O 6 S À Á2H 2 O, (I), and 6-oxo-1,9-dihydropurin-7-ium perchlorate monohydrate, C 5 H 5 N 4 O + ÁClO 4 À ÁH 2 O, (II), have been synthesized and characterized using single-crystal X-ray diffraction and Hirshfeld analysis. In both salts, the hypoxanthine molecule is protonated at the N7 position of the purine ring. In salt (I), the cation and anion are connected through N-HÁ Á ÁO interactions. The protonated hypoxanthine cations of salt (I) form base pairs with another symmetry-related hypoxanthine cation through N-HÁ Á ÁO hydrogen bonds with an R 2 2 (8) ring motif, while in salt (II), the hypoxanthine cations are paired through a water molecule via N-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds with an R 3 3 (11) ring motif. The packings within the crystal structures are stabilized bystacking interactions in salt (I) and C-OÁ Á Á interactions in salt (II). The combination of several interactions leads to the formation of supramolecular sheets extending parallel to (010) in salts (I) and (II). Hirshfeld surface analysis and fingerprint plots reveal that OÁ Á ÁH/HÁ Á ÁO contacts play the major role in the crystal packing of each of the salts, with a 54.1% contribution in salt (I) and 62.3% in salt (II).
Hypoxanthine (HX), a potential oxygen-free radical generator, is a strong agent against cancer cells (Susithra et al., 2018;Latosiń ska et al., 2014;Rutledge et al., 2007). The presence of the imine group in its structure is responsible for its pharmacological activity. Hypoxanthine can exist in two stable tautomers, viz. as the oxo-N7(H) form and as the oxo-N9(H) form. When hypoxanthine interacts with strong acids, it becomes protonated at position N7 or N9. A limited number of hypoxanthine salts like hypoxanthine nitrate (Cabaj & Dominiak, 2021;Cabaj et al., 2019) and hypoxanthine hydrochloride monohydrate (Sletten & Jensen, 1969) have been reported so far in the literature.
The current article reports the crystal structures of hypoxanthinium 5-sulfosalicylate dihydrate, (I), and hypoxanthinium perchlorate monohydrate, (II), salts and the noncovalent interactions that govern their crystal packings.
Salt (II) crystallizes with one hypoxanthinium cation, one perchlorate anion (PCA À ) and one solvent water molecule in the asymmetric unit. The molecular structure of salt (II) is shown in Fig. 2. Again, the N7 atom of the purine ring is protonated, as confirmed by the widening of the C5-N7-C8 angle to 108.00 (12) . The N3-C4-C5-N7 torsion angle of 179.34 (14) is similar to the values determined for salt (I). The PCA À anion has the characteristic tetrahedral shape, with Cl-O bond lengths between 1.4116 (15) and 1.4421 (15) Å , and O-Cl-O angles between 108.29 (9) and 111.24 (12) .

Figure 2
The asymmetric unit of salt (II), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonding.

Figure 1
The asymmetric unit of salt (I), showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate hydrogen bonding and the disorder of cation B + is shown.

Figure 6
The alternating arrangement of cationic and anionic sheets in salt (I).

Figure 5
The supramolecular layer of assembled 5SCA À anions in salt (I).
research communications Table 3 Comparison of salt forms of purine derivatives containing halides/nitrate/phosphite/phosphate/sulfate and perchlorates as anions.

Compound
Space group Primary interaction between Graph-set motif

Figure 9
A view of the PCA À anions and water molecules connecting sheets through O-HÁ Á ÁO hydrogen bonds and a view of the C-OÁ Á Á interactions ( = imidazole and pyrimidine rings of the cation) in salt (II).

Figure 10
Hirshfeld surface for salts (a) (I) and (b)      Primary ring motifs observed in purine derivatives.  (Bishop et al., 2014). In general, salts of structurally similar systems will have similar molecular recognition patterns and supramolecular motifs. However, for salts (I) and (II) and related systems compiled in Table 3, great similarities are not observed. The differences in molecular recognition and supramolecular self-assembly might be due to the involvement of other functional groups or substituents in the structures, the intrusion of water molecules in the crystal structure, or the ratio of anions and cations present in the asymmetric unit.

Synthesis and crystallization
Salt (I) was synthesized by mixing an equimolar ratio of hypoxanthine (0.0340 g) and 5-sulfosalicylic acid (0.0545 g) in hot water. The solution was heated to 333 K for 1 h and then allowed to cool slowly to room temperature. Colourless needle-shaped crystals were harvested from the mother liquid after one week. Salt (II) was synthesized by mixing an equimolar ratio of hypoxanthine (0.0340 g) and iron perchlorate monohydrate (0.0681 g) in hot water. The solution was heated to 333 K with constant stirring for 1 h and then allowed to cool slowly to room temperature. Colourless plate-like crystals were harvested from the mother liquid after one week. Secondary ring motifs observed in purine derivatives.

Refinement
Crystal data, data collection and structure refinement details of salts (I) and (II) are summarized in Table 4. In salt (I), carbon (C5 and C6) and oxygen (O6) atoms of cation B are equally disordered over two sets of sites, with a refined occupancy ratio of 0.503 (18):0.497 (18). The solvent water molecule O3W is disordered over two positions, with a refined site-occupancy ratio of 0.58 (6):0.42 (6). The H atoms of water molecules O1W and O2W were located from a difference Fourier map, and the O-H distance restrained to 0.82 Å . Attempts to localize the H atoms of O3W and O4W in (I) from difference Fourier maps failed as there were no relevant electron densities close to these atoms. Hence, these H atoms are not part of the model but are included in the formula. All C-and N-bound H atoms in (I) were placed in idealized positions and refined freely using a riding model, with C-H = 0.95 Å and N-H = 0.86 Å , and with U iso (H) = 1.2U eq (C,N). In salt (II), the N-bound H atoms were located in a difference Fourier map and refined freely. The H atoms of the water molecule were likewise located from a difference Fourier map. The geometry of the water molecule was restrained using DFIX commands with an O-H distance of 0.85 Å and an HÁ Á ÁH distance of 1.36 Å . All C-bound H atoms were treated as for salt (I). POVRay (Cason, 2004); software used to prepare material for publication: PLATON (Spek, 2020) and publCIF (Westrip, 2010). Extinction correction: SHELXL (Sheldrick, 2015b), Fc * =kFc[1+0.001xFc 2 λ 3 /sin(2θ)] -1/4

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq Occ. ( 0.058 (7) 0.077 (7) 0.026 (4) −0.009 (7 (5) (6)  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.